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A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway.

TitleA Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway.
Publication TypeJournal Article
Year of Publication2007
AuthorsO'Carroll D, Mecklenbrauker I, Das PPratim, Santana A, Koenig U, Enright AJ, Miska EA, Tarakhovsky A
JournalGenes Dev
Volume21
Issue16
Pagination1999-2004
Date Published2007 Aug 15
ISSN0890-9369
KeywordsAnimals, Argonaute Proteins, B-Lymphocytes, Cell Line, Erythroblasts, Erythropoiesis, Eukaryotic Initiation Factor-2, Gene Expression Regulation, Developmental, Hematopoiesis, Lymphopoiesis, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs
Abstract

Binding of microRNA (miRNA) to mRNA within the RNA-induced silencing complex (RISC) leads to either translational inhibition or to destruction of the target mRNA. Both of these functions are executed by Argonaute 2 (Ago2). Using hematopoiesis in mice as a model system to study the physiological function of Ago2 in vivo, we found that Ago2 controls early development of lymphoid and erythroid cells. We show that the unique and defining feature of Ago2, the Slicer endonuclease activity, is dispensable for hematopoiesis. Instead, we identified Ago2 as a key regulator of miRNA homeostasis. Deficiency in Ago2 impairs miRNA biogenesis from precursor-miRNAs followed by a reduction in miRNA expression levels. Collectively, our data identify Ago2 as a highly specialized member of the Argonaute family with an essential nonredundant Slicer-independent function within the mammalian miRNA pathway.

DOI10.1101/gad.1565607
Alternate JournalGenes Dev.
PubMed ID17626790
PubMed Central IDPMC1948855
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